Beta-turns have been strongly implicated as key recognition sites which trigger complex immunologic, metabolic, genomic and endocrinologic events. The proposed investigation involves probing the structure activity relationship of erabutoxin b, the venom protein of the sea snake Laticauda Semifasciata, which specifically inhibits nicotinic cholinergic transmission in a nondepolarizing curare-like manner. The design, synthesis and pharmacological evaluation of conformationally restricted nonpeptide mimetics of the beta-turn region of erabutoxin b, containing the proposed essential residues for neurotoxic activity that are invariant in all cholinergic neurotoxic snake venoms, is detailed. Our designed mimetics should provide a unique opportunity to critically probe and quantitate the contributions of the key residues involved in the binding of erabutoxin to the AcChoR. Moreover, the significance of the proposed research extends far beyond the development of a novel approach to investigate the ligand binding properties of this receptor protein. The synthetic strategies discussed in this proposal would allow for the incorporation of any of the amino acid side chain functionalities as components of our mimetic. Additionally the ability to generate peptide hybrids, i.e. syntheitic turns coupled to oligopeptide chains, would open several exciting avenues of exploration. Therefore, the ability to mimic the activity of the 62 amino acid protein erabutoxin b with small, synthetic model would augur well for the expanded application of these methods to investigate additional critical biochemical issues. Beyond these fundamental questions, the therapeutic ramification of this research could prove profound. Peptides have severe limitations as drug candidates. Metabolic instability, lack of specificity, and low bioavailability are all serious liabilities. Peptide mimetics should be devoid of many if not all of these handicaps.